Dopamine is an important neurotransmitter in the central nervous system (CNS), where it has been shown to be involved with motor function, perception, arousal, motivation and emotion. Accordingly, dopamine dysfunction has been shown to play an important role in a number of CNS-related disorders including psychotic disorders, movement disorders, schizophrenia, Parkinson's disease, drug abuse, eating disorders, cognition and memory disorders, depression, sexual dysfunction, and others. Dopamine has also been shown to play an important role in the peripheral nervous system, where it has been associated with the control of blood to the kidneys and in autonomic ganglion transmission.
Dopamine receptors in the CNS have traditionally been divided into two general categories, designated D1 and D2 receptors, based on biochemical and pharmacological differences between the two receptor types. Further, additional dopamine receptors have been identified and defined through molecular cloning techniques. For example, the D3 and D4 receptors have been described and are classified as D2-like, and the D5 receptor has been described and exhibits D1-like receptor pharmacology.
Conformationally restricted analogs of dopamine have also been reported in U.S. Pat. Nos. 5,047,536, 5,420,134, 6,194,423, 6,413,977, and 5,597,832, the disclosures of which are incorporated herein by reference.